Neurotransmitter Depletion Research Articles

Transmission of temporally correlated spike trains through synapses with short-term depression.

Short-term synaptic depression, caused by depletion of releasable neurotransmitter, modulates the strength of neuronal connections in a history-dependent manner. Quantifying the statistics of synaptic transmission requires stochastic models that link probabilistic neurotransmitter release with presynaptic spike-train statistics. Common approaches are to model the presynaptic spike train as either regular or a memory-less Poisson process: few analytical results are available that describe depressing synapses when the afferent spike train has more complex, temporally correlated statistics such as bursts. Here we present a series of analytical results—from vesicle release-site occupancy statistics, via neurotransmitter release, to the post-synaptic voltage mean and variance—for depressing synapses driven by correlated presynaptic spike trains. The class of presynaptic drive considered is that fully characterised by the inter-spike-interval distribution and encompasses a broad range of models used for neuronal circuit and network analyses, such as integrate-and-fire models with a complete post-spike reset and receiving sufficiently short-time correlated drive. We further demonstrate that the derived post-synaptic voltage mean and variance allow for a simple and accurate approximation of the firing rate of the post-synaptic neuron, using the exponential integrate-and-fire model as an example. These results extend the level of biological detail included in models of synaptic transmission and will allow for the incorporation of more complex and physiologically relevant firing patterns into future studies of neuronal networks.

Neurotransmitter Depletion in Early Epileptic Encephalopathies and Possible Therapeutic Options

Neurotransmitter Depletion in Early Epileptic Encephalopathies and Possible Therapeutic Options

Immunometabolism: T cells activate the fear.

T cell activation is associated with a depletion of amino acids and neurotransmitters and may result in behavioural changes

Efficacy and safety of AAV2 gene therapy in children with aromatic L-amino acid decarboxylase deficiency: an open-label, phase 1/2 trial

Aromatic l-amino acid decarboxylase (AADC) deficiency is an inherited disease that causes depletion of neurotransmitters and severe motor dysfunction in infants and children. We previously reported compassionate use of an adeno-associated virus (AAV) vector containing the human AADC gene (AAV2-hAADC) in four children with AADC deficiency (aged 4-6 years). In this study, we aimed to establish the efficacy and safety of this treatment. We did an open-label, phase 1/2 trial at the National Taiwan University Hospital (Taipei, Taiwan). We included patients who had a definitive diagnosis and clinical symptoms of AADC deficiency (hypotonia, dystonia, and oculogyric crisis), who were older than 24 months or had skull bones suitable for stereotactic surgery, and who had an anti-AAV2 antibody titre lower than 1·0 optical density. All patients received bilateral intraputaminal injections of AAV2-hAADC (1·81 × 1011 vg in total) through stereotactic brain surgery. Primary efficacy outcomes were an increase in the Peabody Developmental Motor Scales (second edition; PDMS-2) score of greater than 10 points and an increase in homovanillic acid (HVA) or 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid 12 months after gene therapy. We assessed patients at baseline and at 3, 6, 9, and 12 months after gene therapy, and every 6 months thereafter for one further year; all patients who received the treatment were included in the analysis. We assessed for surgical complications (cerebrospinal fluid leakage and intracerebral haemorrhage) at days 3-7 after AAV2 gene therapy, and we assessed adverse events during the follow-up evaluations for 12 months. This study is registered with ClinicalTrials.gov, number NCT01395641. Ten patients (median age 2·71 years, IQR 2·46-6·35) were enrolled from Oct 1, 2014, to Dec 2, 2015. All patients tolerated the surgeries and vector injections. One patient died from influenza B encephalitis during an endemic outbreak 10 months after treatment; therefore, 9 months of data were included in the analyses for this patient. All patients met the primary efficacy endpoint: 12 months after gene therapy, PDMS-2 scores were increased by a median of 62 points (IQR 39-93; p=0·005) and HVA concentrations by a median of 25 nmol/L (IQR 11-48; p=0·012); however, there was no significant change in 5-HIAA concentrations (median difference 0, IQR 0-5; p=0·20). In total, 101 adverse events were reported, with the most common being pyrexia (16 [16%] of 101 events) and orofacial dyskinesia (ten [10%]). 12 serious adverse events occurred in six patients, including one death (treatment-unrelated encephalitis due to influenza B infection), one life-threatening pyrexia, and ten events that led to hospital admission. Transient post-gene therapy dyskinesia occurred in all patients but was resolved with risperidone. Of 31 treatment-related adverse events, only one (patient 1) was severe in intensity, and none led to hospital admission or death. Our findings suggest that intraputaminal injection of AAV2-hAADC is well tolerated and might improve motor development in children with AADC deficiency. AADC Research Fund at National Taiwan University Hospital and the National Research Programme for Biopharmaceuticals.

Contractile properties of periosteal arterioles in the guinea-pig tibia.

The periosteal arterioles of the compact bone may play a critical role in bone growth. To explore the contractile properties of tibial arterioles, spontaneous and nerve-evoked constrictions were compared in preparations from 3-week-old and 1-year-old guinea-pigs. Changes in arteriole diameters were measured using video microscopy. Their innervation was investigated using fluorescence immunohistochemistry. Fifty per cent and 40% of tibial arterioles from 3-week-old and 1-year-old guinea-pigs, respectively, exhibited spontaneous phasic constrictions that were inhibited by 1μM nifedipine, 10μM cyclopiazonic acid or 100μM 2-APB. Nerve-evoked phasic constrictions in both age groups were largely suppressed by phentolamine (1μM), an α-adrenoceptor antagonist, or sympathetic neurotransmitter depletion using guanethidine (10μM) but were enhanced by spanttide (1μM), a substance P receptor antagonist, or L-nitro arginine (L-NA; 100μM), an inhibitor of nitric oxide synthase (NOS). Nerve-evoked constrictions in 1-year-old animals were smaller than those in younger animals but greatly enhanced by L-NA. Immunohistochemistry revealed sympathetic and substance P-positive primary afferent nerves running along the arterioles as well as endothelial NOS expression in both age groups. Spontaneous arteriolar constrictions appear to rely on both Ca2+ release from the sarcoplasmic reticulum and Ca2+ influx through L-type Ca2+ channels. Noradrenaline released from sympathetic nerves triggers arteriolar constriction, while substance P released from primary afferent nerves dilates the arterioles by releasing nitric oxide (NO), presumably from the endothelium. Thus, the enhanced endothelial NO release in adult guinea-pigs may be important to increase the blood supply to meet the increased metabolic demands during bone growth.

FMRI study of the role of glutamate NMDA receptor in the olfactory adaptation in rats: Insights into cellular and molecular mechanisms of olfactory adaptation

Olfactory adaptation, characterized by attenuation of response to repeated odor stimulations or continuous odor exposure, is an intrinsic feature of olfactory processing. Adaptation can be induced by either “synaptic depression” due to depletion of neurotransmitters, or “enhanced inhibition” onto principle neurons by local inhibitory interneurons in olfactory structures. It is not clear which mechanism plays a major role in olfactory adaptation. More importantly, molecular sources of enhanced inhibition have not been identified. In this study, olfactory responses to either repeated 40-s stimulations with interstimulus intervals (ISI) of 140-s or 30-min, or a single prolonged 200-s stimulus were measured by fMRI in different naïve rats. Olfactory adaptations in the olfactory bulb (OB), anterior olfactory nucleus (AON), and piriform cortex (PC) were observed only with repeated 40-s odor stimulations, and no olfactory adaptations were detected during the prolonged 200-s stimulation. Interestingly, in responses to repeated 40-s odor stimulations in the PC, the first odor stimulation induced positive activations, and odor stimulations under adapted condition induced negative activations. The negative activations suggest that “sparse coding” and “global inhibition” are the characteristics of olfactory processing in PC, and the global inhibition manifests only under an adapted condition, not a naïve condition. Further, we found that these adaptations were NMDA receptor dependent; an NMDA receptor antagonist (MK801) blocked the adaptations. Based on the mechanism that glutamate NMDA receptor plays a role in the inhibition onto principle neurons by interneurons, our data suggest that the olfactory adaptations are caused by enhanced inhibition from interneurons. Combined with the necessity of the interruption of odor stimulation to observe the adaptations, the molecular source for the enhanced inhibition is most likely an increased glutamate release from presynaptic terminals due to glutamate over-replenishment during the interruption of odor stimulation. Furthermore, with blockage of the adaptations, the data reveal that orbital, medial & prefrontal, and cingulate cortices (OmPFC) are involved in the olfactory processing.

Probiotics as an Adjuvant Therapy in Major Depressive Disorder.

BackgroundMajor depressive disorder is a common, debilitating psychiatric disorder, which originates from the interaction of susceptibility genes and noxious environmental events, in particular stressful events. It has been shown that dysregulation of hypothalamus-pituitary-adrenal (HPA) axis, imbalance between anti- and pro-inflammatory cytokines, depletion of neurotransmitters (serotonin, norepinephrine and/or dopamine) in the central nervous system, altered glutamatergic and GABAergic transmission have an important role in the pathogenesis of depression. Due to numerous diverse biological events included in the pathophysiology of depression a large number of antidepressant drugs exerting distinct pharmacological effects have been developed. Nevertheless, clinical needs are still not solved.ResultsRelatively new research strategies advanced the understanding of psychiatric illness and their connections with disturbances in gastrointestinal tract. The existence of bidirectional communication between the brain and the gut has been proven, and an increasing body of evidence supports the hypothesis that cognitive and emotional processes are influenced through the brain-gut axis. On the other hand, microbiome may influence brain function and even behavior giving to the specific microorganisms a psychobiotic potential.ConclusionsIn this review we discuss the possibilities of classical antidepressant drug treatment being supported with the psychobiotics/probiotic bacteria in patients suffering from major depressive disorder.

Assessment of Acetylcholinestrase Inhibiton by Bacopa Monneiri and Acephate in Hippocampus of Chick Brain for Impediment of Alzheimer’s Disease

1. Abstract 1.1. Introduction: In Alzheimer’s disease (AD), a depletion of the neurotransmitter, acetylcholine (ACh) occurs due to the destruction of cholinergic neurons. By inhibiting Acethylcholinesterase (AChE), the enzyme which catalyses break down of ACh, levels of this neurotransmitter can be elevated and function may be improved. 1.2. Objective: This study sought to find out whether the Acethylcholinesterase (AChE) activity, enzyme kinetics and histology in the hippocampus of Chick brain were affected in a selective manner by a herbal extract, and organophosphate Pesticide and combination of both: a. Ethanol extract of Bacopa monneiri b. Acephate c. Pretreatment of ethanol extract of Bacopa followed by acephate. 1.3. Method: AChE activity was determined by Ellman’s method and AChE kinetics by LB plots. 1.4. Result: AChE activities due to Bacopa monneiri, acephate and combination of both in hippocampus of treated chicks were significantly inhibited to 72%, 70.9% and 94% respectively. Our kinetic study reveals that acephate is competitive while Bacopa monneiri was competitive-noncompetitive inhibitor of AChE. Slight histological variation was observed as the concentration of cytoplasm of CA1 and CA3 pyramidal cell layers in the Hippocampus of chick treated with acephate and ethanolic extract of Bocopa monnieri. 1.5. Conclusion: Common herb Bacopa monneri may help to improve ACh level, but scientific evidence to prove that it can treat Alzheimer's disease, is still to confirm.

Enhancing speech envelope by integrating hair-cell adaptation into cochlear implant processing

Cochlear implants (CIs) bypass some of the mechanisms that underlie normal neural behavior as occurs in acoustic hearing. One such neural mechanism is short-term adaptation, which has been proposed to have a significant role in speech perception. Acoustically-evoked neural adaptation has been mainly attributed to the depletion of neurotransmitter in the hair-cell to auditory-nerve synapse and is therefore not fully present in CI stimulation. This study evaluated a signal processing method that integrated a physiological model of hair-cell adaptation into CI speech processing. The linear high-pass adaptation process expanded the range of rapid variations of the electrical signal generated by the clinical processing strategy. Speech perception performance with the adaptation-based processing was compared to that of the clinical strategy in seven CI users. While there was large variability across subjects, the new processing improved sentence recognition and consonant identification scores in quiet in all the tested subjects with an average improvement of 8% and 6% respectively. Consonant recognition scores in babble noise were improved at the higher signal-to-noise ratios tested (10 and 6 dB) only. Information transfer analysis of consonant features showed significant improvements for manner and place of articulation features, but not for voicing. Enhancement of within-channel envelope cues was confirmed by consonant recognition results obtained with single-channel strategies that presented the overall amplitude envelope of the signal on a single active electrode. Adaptation-inspired envelope enhancement techniques can potentially improve perception of important speech features by CI users.

Emotional Stress as a Risk for Hypertension in Sub-Saharan Africans: Are We Ignoring the Odds?

Globally most interventions focus on improving lifestyle habits and treatment regimens to combat hypertension as a non-communicable disease (NCD). However, despite these interventions and improved medical treatments, blood pressure (BP) values are still on the rise and poorly controlled in sub-Saharan Africa (SSA). Other factors contributing to hypertension prevalence, such as chronic emotional stress, might provide some insight for future health policy approaches.Currently, Hypertension Society guidelines do not mention emotional stress as a probable cause for hypertension. Recently the 2014 World Global Health reports, suggested that African governments should consider using World Health Organization hypertension data as a proxy indicator for social well-being. However, the possibility that a stressful life and taxing environmental factors might disturb central neural control of BP regulation has largely been ignored in SSA.Linking emotional stress to vascular dysregulation is therefore one way to investigate increased cardiometabolic challenges, neurotransmitter depletion and disturbed hemodynamics. Disruption of stress response pathways and subsequent changes in lifestyle habits as ways of coping with a stressful life, and as probable cause for hypertension prevalence in SSA, may be included in future preventive measures. We will provide an overview on emotional stress and central neural control of BP and will include also implications thereof for clinical practice in SSA cohorts.

Cholinergic mechanisms of high-frequency stimulation in entopeduncular nucleus.

Chronic, high-frequency (>100 Hz) electrical stimulation, known as deep brain stimulation (DBS), of the internal segment of the globus pallidus (GPi) is a highly effective therapy for Parkinson's disease (PD) and dystonia. Despite some understanding of how it works acutely in PD models, there remain questions about its mechanisms of action. Several hypotheses have been proposed, such as depolarization blockade, activation of inhibitory synapses, depletion of neurotransmitters, and/or disruption/alteration of network oscillations. In this study we investigated the cellular mechanisms of high-frequency stimulation (HFS) in entopeduncular nucleus (EP; rat equivalent of GPi) neurons using whole cell patch-clamp recordings. We found that HFS applied inside the EP nucleus induced a prolonged afterdepolarization that was dependent on stimulation frequency, pulse duration, and current amplitude. The high frequencies (>100 Hz) and pulse widths (>0.15 ms) used clinically for dystonia DBS could reliably induce these afterdepolarizations, which persisted under blockade of ionotropic glutamate (kynurenic acid, 2 mM), GABAA (picrotoxin, 50 μM), GABAB (CGP 55845, 1 μM), and acetylcholine nicotinic receptors (DHβE, 2 μM). However, this effect was blocked by atropine (2 μM; nonselective muscarinic antagonist) or tetrodotoxin (0.5 μM). Finally, the muscarinic-dependent afterdepolarizations were sensitive to Ca(2+)-sensitive nonspecific cationic (CAN) channel blockade. Hence, these data suggest that muscarinic receptor activation during HFS can lead to feedforward excitation through the opening of CAN channels. This study for the first time describes a cholinergic mechanism of HFS in EP neurons and provides new insight into the underlying mechanisms of DBS.

Use of ligand-based pharmacophore modeling and docking approach to find novel acetylcholinesterase inhibitors for treating Alzheimer's

Alzheimer's disease is a neurological disorder in which the patient suffers from memory loss and impaired cognitive abilities. Though the main cause of the disease is not yet known, depletion of neurotransmitter at synaptic junctions, accumulation of insoluble beta amyloid plaques and neurofibrillary tangles are the main pathologies associated with it. The FDA approved drugs for alzheimer's belong to the category of acetylcholinesterase inhibitors. But most of the drugs have been observed to be associated with adverse side effects. In this study, we have developed a pharmacophore (responsible for interaction with acetylcholinesterase active site) based on the already existing drugs and drug candidates. This pharmacophore was used to search for novel AChE inhibitors with altogether different chemical scaffold using high throughput virtual screening and docking studies. Finally, we have reported two compounds, OPA and OMT, which possess high affinity for catalytic site of AChE enzyme and thus, can be considered as potential AChE inhibitors for the symptomatic treatment of Alzheimer's.

Nutritional Deficiencies Associated with Obesity

Obesity is a serious problem in the United States and developing countries. Obesity leads not only to serious chronic health problems but is also associated with approximately 40% higher health care costs than normal weight individuals. Long standing theories of weight loss rested on the simplistic idea that one must expend more calories than one consumes. Although this is a mainstay of weight loss regimens, the underlying causes of obesity are more complex than previously considered. Research has noted nutritional deficiencies in subjects that are overweight, obese and morbidly obese. Is the cause of this contradictory deficiency due to low-cost, nutrient poor food or do findings suggest that there is an alteration in absorption, distribution, metabolism and/or excretion of these nutrients in overweight and obese individuals. Nutrient deficiencies in obese populations are very common with vitamin D deficiency being the most prevalent affecting approximately 57-94% of obese individuals. Interestingly, correction by protein-rich diet supplementation containing vitamins and minerals did not correct levels. In contrast, micronutrient levels remained low or became even lower. This discrepancy may be explained by gastrointestinal barrier dysfunction, intestinal microbiota or increased metabolic demand. There are also theories examining amino acid and neurotransmitter depletion that disrupts feedback mechanisms. There are several neurotransmitters that regulate weight, appetite and satiety. Findings suggest that a low level of neurotransmitters, amino acid precursors or receptors had a direct impact on a subject's weight. The review of research reveals that obesity is a complex problem with multiple contributing factors. Further understanding of the dietary deficiencies and the regulation of the metabolic pathway is fundamental towards effective treatment.

Effects of the aqueous extract of Schizandra chinensis fruit on ethanol withdrawal-induced anxiety in rats.

We previously demonstrated that the aqueous extract of the Schizandra chinensis fruit (AESC) ameliorated Cd-induced depletion of monoamine neurotransmitters in the brain through antioxidant activity. In the present study, we investigated the effect of AESC on anxiety-like behavior and the levels of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol (a metabolite of norepinephrine) in different brain regions during ethanol withdrawal in rats. Male Sprague-Dawley rats were treated with 3 g/kg of ethanol (20%, w/v) or saline by daily intraperitoneal injection for 28 days followed by three days of withdrawal. During withdrawal, rats were given AESC (100 mg × kg(-1)× d(-1) or 300 mg × kg(-1)× d(-1), P.O.) once a day for three days. Thirty minutes after the final dose of AESC, the anxiogenic response was evaluated using an elevated plus maze, and the plasma corticosterone levels were examined by radioimmunoassay. Meanwhile, the concentrations of norepinephrine and 3-methoxy-4-hydroxy-phenylglycol in the hypothalamic paraventricular nucleus and hippocampus were also measured by high performance liquid chromatography. Rats undergoing ethanol withdrawal exhibited substantial anxiety-like behavior, which was characterized by both the decrease in time spent in the open arms of the elevated plus maze and the increased level of corticosterone secretion, which were greatly attenuated by doses of AESC in a dose-dependent manner. The high performance liquid chromatography analysis revealed that ethanol withdrawal significantly increased norepinephrine and 3-methoxy-4-hydroxy-phenylglycol levels in the hypothalamic paraventricular nucleus, while not significantly altering them in the hippocampus. Similar to the results from the elevated plus maze test, the AESC significantly inhibited the elevation of norepinephrine and its metabolite in the hypothalamic paraventricular nucleus in a dose-dependent manner. These results suggest that AESC attenuates anxiety-like behavior induced by ethanol withdrawal through modulation of the hypothalamic norepinephrine system in the brain.

Palliative medicine specialists’ causal explanations for depression in the palliative care setting: a qualitative in-depth interview study

ObjectiveMedical practitioners have different causal explanations for depression, and may have greater difficulty in explaining causality of depression in the palliative care setting. The objective of this study was to...

Recent updates in the treatment of neurodegenerative disorders using natural compounds.

Neurodegenerative diseases are characterized by protein aggregates and inflammation as well as oxidative stress in the central nervous system (CNS). Multiple biological processes are linked to neurodegenerative diseases such as depletion or insufficient synthesis of neurotransmitters, oxidative stress, abnormal ubiquitination. Furthermore, damaging of blood brain barrier (BBB) in the CNS also leads to various CNS-related diseases. Even though synthetic drugs are used for the management of Alzheimer's disease, Parkinson's disease, autism, and many other chronic illnesses, they are not without side effects. The attentions of researchers have been inclined towards the phytochemicals, many of which have minimal side effects. Phytochemicals are promising therapeutic agents because many phytochemicals have anti-inflammatory, antioxidative as well as anticholinesterase activities. Various drugs of either synthetic or natural origin applied in the treatment of brain disorders need to cross the BBB before they can be used. This paper covers various researches related to phytochemicals used in the management of neurodegenerative disorders.

The role of inflammatory cytokines on the aetiopathogenesis of depression

The primary focus of this review is to provide an overview of the role of inflammation in the development of depression. The article will describe how inflammatory cytokines contribute to depression via action on three major pathways in the brain: the neuroendocrine; neurotransmitter depletion; and neuroprogression pathways. An online literature search was carried out in July 2012. Original articles and reviews were selected if they discussed the role of inflammation on the development of depression. There is a large body of current research on the role of inflammatory cytokines on the development of depression. Cytokines have been found to interact with different pathways in the brain, and may contribute to the development of depression. Cytokines cause hypercortisolaemia by dysregulation of the hypothalamic-pituitary-adrenal axis directly by activating it and indirectly by modifying glucocorticoid receptor sensitivity to cortisol leading to cortisol hypersecretion. Cytokines deplete central synaptic serotonin levels by reducing its synthesis and increasing its reuptake. They may also deplete neurotrophic factors which are believed to play a neuroprotective role against depression. Cytokines activate cellular cascades that cause excitotoxicity and apoptosis and inhibit neurogenesis in the hippocampus. There is a growing body of correlative studies that suggest inflammatory cytokines may be a central factor that can affect multiple neuronal pathways and have an additive effect on the development of depression. However, the fact that not all people with inflammatory conditions suffer from depression suggests that depression is not purely a result of elevated inflammatory cytokines. Depression may be a result of a complex pathology that remains an area of growing interest and importance.

Acute Suppression of Spontaneous Neurotransmission Drives Synaptic Potentiation

The impact of spontaneous neurotransmission on neuronal plasticity remains poorly understood. Here, we show that acute suppression of spontaneous NMDA receptor-mediated (NMDAR-mediated) neurotransmission potentiates synaptic responses in the CA1 regions of rat and mouse hippocampus. This potentiation requires protein synthesis, brain-derived neurotrophic factor expression, eukaryotic elongation factor-2 kinase function, and increased surface expression of AMPA receptors. Our behavioral studies link this same synaptic signaling pathway to the fast-acting antidepressant responses elicited by ketamine. We also show that selective neurotransmitter depletion from spontaneously recycling vesicles triggers synaptic potentiation via the same pathway as NMDAR blockade, demonstrating that presynaptic impairment of spontaneous release, without manipulation of evoked neurotransmission, is sufficient to elicit postsynaptic plasticity. These findings uncover an unexpectedly dynamic impact of spontaneous glutamate release on synaptic efficacy and provide new insight into a key synaptic substrate for rapid antidepressant action.

Degradation of stored movement representations in the parkinsonian brain and the impact of levodopa

Parkinson's disease (PD) results from the depletion of dopamine and other neurotransmitters within the basal ganglia, and is typically characterized by motor impairment (e.g., bradykinesia) and difficulty initiating voluntary movements. Difficulty initiating a movement may result from a deficit in accessing or executing a stored representation of the movement, or having to create a new representation each time a movement is required. To date, it is unclear which may be responsible for movement initiation impairments observed in PD. In this study, we used functional magnetic resonance imaging and a task in which participants passively viewed familiar and unfamiliar graspable objects, with no confounding motor task component. Our results show that the brains of PD patients implicitly analyze familiar graspable objects as if the brain has little or no motor experience with the objects. This was observed as a lack of differential activity within brain regions associated with stored movement representations for familiar objects relative to unfamiliar objects, as well as significantly greater activity for familiar objects when off levodopa relative to on medication. Symptom severity modulated this activity difference within the basal ganglia. Levodopa appears to normalize brain activity, but its effect may be one of attenuation of brain hyperactivity within the basal ganglia network, which is responsible for controlling motor behavior and the integration of visuomotor information. Overall, this study demonstrates that difficulty initiating voluntary movements experienced by PD patients may be the result of degradation in stored representations responsible for the movement.

Advances with MRI in Parkinson disease

Degeneration of dopamine neurons in the substantia nigra and intracellular deposition of Lewy body inclusions are the pathologic hallmarks of Parkinson disease (PD). Depletion of dopamine and other neurotransmitters results in motor (rest tremor, bradykinesia, and rigidity) and nonmotor (cognitive impairment, sleep disorders, fatigue, and depression) symptoms.